FeCl_3诱导的大鼠颈总动脉血栓模型血浆TXA_2、PGI_2、抗凝和纤溶活性的变化

Changes of TXA_2 and PGI_2 content and anticoagulative and fibrinolytic activity in the plasma in a rat model of topical FeCl_3-induced carotid artery thrombosis

目的探讨FeC l3诱导的大鼠动脉血栓形成模型血浆TXA2、PG I2含量及抗凝、纤溶活性的变化。方法以FeC l3外敷诱导大鼠左侧颈总动脉血栓形成,测定血浆TXA2和PG I2稳定代谢产物TXB2、6-keto-PGF1α含量及t-PA、PAI-1、PLG、AT-Ⅲ和PC活性。结果浓度为2.16 mol.L-1的FeC l3可诱导大鼠颈总动脉闭塞性血栓形成,且该模型血浆TXB2含量升高(P<0.05),6-keto-PGF1α含量降低(P<0.05);血浆t-PA和PLG活性降低(P<0.05),PAI-1活性无变化(P>0.05),t-PA/PAI-1比值降低(P<0.05);血浆AT-Ⅲ活性降低(P<0.01),PC活性轻微降低(0.10>P>0.05)。噻氯匹定可抑制FeC l3诱导的血栓形成,但对TXB2和6-keto-PGF1α无影响,表明其抗栓作用不是通过抑制血小板TXA2生成而实现的;噻氯匹定还可升高血浆t-PA活性,可能系该药通过抑制血栓形成,减少了血浆t-PA消耗所致。而该药对AT-Ⅲ和PC活性无影响。抗凝血药低分子肝素(LMWH)也可抑制血栓形成,该药对TXB2和6-keto-PGF1α无影响。LMWH可升高血浆t-PA活性和t-PA/PAI-1比值,可能与其促进血管内皮细胞释放t-PA有关。LMWH还可使该模型血浆AT-Ⅲ活性降低,这是由于LMWH与AT-Ⅲ结合而发挥其抗凝作用,从而使血浆中AT-Ⅲ消耗所致。结论FeC l3可诱导大鼠闭塞性动脉血栓形成,该模型与血小板活化和凝血系统激活有关,同时该模型存在抗凝蛋白活性降低和纤溶活性降低的病理改变。

Aim To investigate changes of TXA2 and PGI2 content and anticoagulative and fibrinolytic activity in the plasma in a rat model of topical FeCl3-induced carotid artery thrombosis. Methods Thrombi were induced by topical ferric chloride to left carotid artery in rats. The content of TXB2 and 6-keto-PGF1α （stable metabolite of TXA2 and PGI2, activity of t-PA, PAI-1, PLG, AT-Ⅲ and PC in the plasma in the model of thrombosis were determined. Results Occlusive thrombi were induced by applying FeCl3 （ 2. 16 mol · L^-1） to left carotid artery. The content of TXB2 was increased markedly （P 〈 0. 05 ）, and the content of 6- keto-PGF1α was lower remarkably in the rat plasma （P 〈 0. 05）. Activities of t-PA, PLG and AT-Ⅲ were lower in the plasma（P 〈 0. 05 ,P 〈 0. 01 ）, activity of PAId had no change （P 〉 0. 05 ）, but t-PA/PAI-1 ratio reduced （P 〈 0. 05）. Activity of PC dropped slightly （0. 10 〉 P 〉 0. 05 ）. Ticlopidine could inhibit thrombosis induced by ferric chloride, but it did not influence TXB2 and 6-keto-PGF1α content and activi-ties of AT-Ⅲ and PC in the plasma. Ticlopidine could enhance activity of t-PA in the plasma. It may be related to the decrease of t-PA consumption by inhibiting thrombosis. Antithrombosis action of ticlopidine may not be concerned to inhibiting production of TXB2 of platelet. LMWH could inhibit thrombosis also, but it did not influence TXB2 and 6-keto-PGF1α content in the plasma. LMWH could enhance activities of t-PA and t- PA/PAI-1 ratio, which may be related to the promoting release of t-PA in vascular endothelial cells. LMWH could reduce activity of AT-Ⅲ, which may be concerned with combination of LMWH and AT-m result in AT-Ⅲ consumption. Conclusion Ferric chloride may induce occlusive thrombosis in rats. Thrombosis may be associated with activation of platelet and blood coagulation system, lower of anticoagulative protein and fibrinolytic activity.